Posts

Testing ChatGPT for cell type recognition 2024-03-25T19:59:49.183Z
Will no one rid me of this turbulent pest? 2023-10-14T15:27:21.497Z
Playing the game vs. finding a cheat code 2023-09-10T18:11:56.077Z
Stomach Ulcers and Dental Cavities 2023-08-05T14:08:15.263Z
Biological DOOM: a brief overview of biological computation 2023-04-29T20:02:25.257Z
My experience getting funding for my biological research 2023-04-16T22:53:33.453Z
Review of “Make People Better” 2023-01-02T20:30:13.218Z
Epigenetics of the mammalian germline 2022-12-23T15:21:37.032Z
What is epigenetics? 2022-11-06T01:24:05.350Z
Gene drives: why the wait? 2022-09-19T23:37:17.595Z
Meiosis is all you need 2022-07-01T07:39:01.547Z

Comments

Comment by Metacelsus on Best in Class Life Improvement · 2024-04-05T06:50:33.382Z · LW · GW

Testosterone will land you in more legal trouble than modafinil.

Comment by Metacelsus on Best in Class Life Improvement · 2024-04-05T06:48:56.983Z · LW · GW

Compounding pharmacies are gray-market. (Buying on "evolutionpeptides.com" would be black-market.)

Comment by Metacelsus on Best in Class Life Improvement · 2024-04-04T09:56:44.439Z · LW · GW

No mention of modafinil? It's quite useful for maintaining productivity on low amounts of sleep.

Comment by Metacelsus on Best in Class Life Improvement · 2024-04-04T09:53:52.606Z · LW · GW

Semaglutide is the real-deal weight loss drug we have been praying for. It works well for 70%+ of people. Losing and keeping weight off is so difficult that prior to ozempic, it was reasonable advice to preach acceptance or extremely restricted diets. Prior to Semaglutide, I used to assume that most of my friends who wanted to lose weight would fail. Now I assume they will trivially succeed if they get on the drugs. Here is how to get on Semaglutide:

  1. I purchased sema, for myself and others, on this site: https://evolutionpeptides.com/products/semaglutide-10mg?variant=42834747326660. It has been a reliable supplier for me. Reliability can always change, but for now, it's where I would go.
  2. Start with a dose of 0.25mg. Increase your dose approximately every four weeks. Stay on lower dosages as long as possible. Tolerance can increase rapidly. For example, the official guidelines say to double your dose after each of the first two months of treatment. I would try to increase dosages more slowly.
  3. Gray market semaglutide is sold as a powder. You need to mix it into a solution to inject. Search for reconstitution solution.
  4. You also need needles. Any insulin needle will work fine but some hurt less than others. Here are the ones I use.
  5. To make the solution, I draw 100 units of reconstitution (a 'full' vial) solution into the needle. I then squirt the solution into the sema vial and repeat this process again. This means 5mg of semaglutide per 200 units of solution. So, to do a 0.25 starting dose, I would inject 10 units of mixed sema solution into my deltoid. It doesn't really matter if you inject into fat or muscle.

Semaglutide feels weird in many ways and makes many people nauseous. Fake Dr. Sapphire's medical advice is to use gray market odansetron to manage nausea. But dramamine is OTC in the USA and most other countries and also works well. Don't expect insanely rapid weight loss. It's normal to lose 1-2 pounds a week, which is honestly quite quick!

 

Injecting anything from the "gray-market" is quite risky, since it may not be sterile. People have died from such things (for example: https://en.wikipedia.org/wiki/New_England_Compounding_Center_meningitis_outbreak)

Comment by Metacelsus on The Best Tacit Knowledge Videos on Every Subject · 2024-04-01T01:31:48.227Z · LW · GW

For biology, JoVE ("Journal of Visual Experiments") is a very good source of videos like this. https://www.jove.com/ Unfortunately it's paywalled.

Comment by Metacelsus on [Linkpost] Practically-A-Book Review: Rootclaim $100,000 Lab Leak Debate · 2024-03-28T21:14:42.164Z · LW · GW

I agree, I think the most likely version of the lab leak scenario does not involve an engineered virus. Personally I would say 60% chance zoonotic, 40% chance lab leak.

Comment by Metacelsus on Testing ChatGPT for cell type recognition · 2024-03-25T20:32:46.950Z · LW · GW

A commenter on my Substack got much better results using Claude 3 Opus.

Comment by Metacelsus on Why correlation, though? · 2024-03-07T16:12:13.219Z · LW · GW

Spearman (rank) correlation is often a good alternative for nonlinear relationships.

Comment by Metacelsus on Cellular respiration as a steam engine · 2024-02-26T18:00:13.380Z · LW · GW

>heats the water (adenosine diphosphate, ADP) to a closely related, higher-energy form (adenosine triphosphate, ATP), which is steam.

I would say protons are the steam, not the ATP/ADP. The electron transport chain "pressurizes" protons by pumping them, and then the protons flow through the ATP synthase "turbine".

Comment by Metacelsus on Everything Wrong with Roko's Claims about an Engineered Pandemic · 2024-02-24T15:23:01.907Z · LW · GW

I think the exact origin of SARS-CoV-2 is a largely irrelevant question. 

Given that it's plausible it could have come either from a wet market or risky biological research, we should shut down both.

(Personally I would say 60% "wet market", 40% "unintentional lab leak")

Comment by Metacelsus on I'd also take $7 trillion · 2024-02-20T23:53:58.136Z · LW · GW

That make sense. If I were going for sarcasm I would have said Kary Mullis.

Comment by Metacelsus on I'd also take $7 trillion · 2024-02-19T19:38:18.257Z · LW · GW

A Nobel-winning scientist like Gregg Semenza would obviously be the best possible expert

 

Funny you should say that . . .
https://retractionwatch.com/2023/10/02/nobel-prize-winner-gregg-semenza-tallies-tenth-retraction/
https://www.nature.com/articles/d41586-022-03032-9
 

Comment by Metacelsus on Childhood and Education Roundup #4 · 2024-01-30T15:40:05.269Z · LW · GW

Emmett Shear on college-level organic chemistry. His experience was that the class was composed of a mix of science track and premed track students. The science students are there to actually learn and retain the material, so even though it’s a massive amount of compounding facts you have to learn, they do fine. Whereas the premed students are happy to do the work, but are thinking of the class as a structural barrier rather than source of information, so they cram rather than retaining information, and then struggle. So it is a question of motivation. How do we get students, across the board, to be motivated by actually caring about the material?

 

As a former TA for organic chemistry, I can definitely confirm this.

Comment by Metacelsus on Making every researcher seek grants is a broken model · 2024-01-26T18:37:56.310Z · LW · GW

As a scientist I strongly agree. It seems like there's been a few steps towards this in recent years, for example with things like the Arc Institute or FROs. Hopefully this model gets the attention of government funders.

Comment by Metacelsus on Notes on Innocence · 2024-01-26T18:32:30.055Z · LW · GW

>I haven’t heard a “Polack joke” in years and I wouldn’t be surprised if the rising generation is mostly unaware that there ever was such a thing.

On the contrary, I heard one at an ACX meetup in Boston in summer 2023. I was not amused.

Comment by Metacelsus on Legalize butanol? · 2023-12-20T16:57:44.405Z · LW · GW

>I think it makes sense for some country with a high rate of alcohol flush reaction to legalize using 1-butanol or oxane as a substitute for ethanol in drinks served at bars and restaurants.

The only downside is that butanol tastes pretty awful.

Comment by Metacelsus on Are There Examples of Overhang for Other Technologies? · 2023-12-14T01:54:18.822Z · LW · GW

I think it would be useful to examine cases where important patents for Input X expired and prices came down quickly, allowing Input X to be used to produce much more of Product Y.

Comment by Metacelsus on re: Yudkowsky on biological materials · 2023-12-13T14:16:03.234Z · LW · GW

That is very wrong. Diamond is hard to make with enzymes because they can't stabilize intermediates for adding carbons to diamond.

 

As a biochemist, I agree.

Comment by Metacelsus on Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible · 2023-12-12T18:52:49.247Z · LW · GW

It does integrate into the genome. It's gene therapy, but not gene editing (which means editing an existing gene).

Comment by Metacelsus on Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible · 2023-12-12T18:52:01.933Z · LW · GW

Consolidating my previous comments:

I discussed this project with GeneSmith and I think it is promising, though very challenging to implement in practice. The hardest part will be safely and efficiently delivering the editing agent to a large fraction of the cells in the brain.

Some other points:

CAR T-cell therapy, a treatment for certain types of cancer, requires the removal of white blood cells via IV, genetic modification of those cells outside the body, culturing of the modified cells, chemotherapy to kill off most of the remaining unmodified cells in the body, and reinjection of the genetically engineered ones. The price is  $500,000 to $1,000,000.

And it only modifies a single gene.

This makes it sound like CAR-T is gene editing, but it isn't. Instead of editing a gene, it introduces a new one (a chimeric T-cell receptor). Although some companies are working on gene editing to enhance CAR-Ts.

I also know of a PHD student in George Church’s lab that was able to make several thousand edits in the same cell at the same time by targeting a gene that has several thousand copies spread throughout the genome.

The paper reporting this was here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229841/

Comment by Metacelsus on Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible · 2023-12-12T18:47:07.199Z · LW · GW
Comment by Metacelsus on Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible · 2023-12-12T18:42:46.882Z · LW · GW

CAR T-cell therapy, a treatment for certain types of cancer, requires the removal of white blood cells via IV, genetic modification of those cells outside the body, culturing of the modified cells, chemotherapy to kill off most of the remaining unmodified cells in the body, and reinjection of the genetically engineered ones. The price is  $500,000 to $1,000,000.

And it only modifies a single gene.

This makes it sound like CAR-T is gene editing, but it isn't. Instead of editing a gene, it introduces a new one (a chimeric T-cell receptor). Although some companies are working on gene editing to enhance CAR-Ts.

Comment by Metacelsus on Accelerating science through evolvable institutions · 2023-12-06T16:13:59.652Z · LW · GW

There's also a lot of statistics that go into designing experiments (rather than analyzing them afterwards). For example, fractional factorial designs, or adaptive clinical trials

Comment by Metacelsus on Why Yudkowsky is wrong about "covalently bonded equivalents of biology" · 2023-12-06T16:11:37.574Z · LW · GW

Yeah, Yudkowsky doesn't know what he's talking about here.

Still, one of the ways protein engineers can make proteins more heat-stable is by adding more covalent bonds (in particular, disulfide crosslinks to prevent unfolding). See the many results for https://scholar.google.com/scholar?q=thermostability+disulfide+bond&hl=en 

Comment by Metacelsus on Accelerating science through evolvable institutions · 2023-12-05T03:18:39.870Z · LW · GW

Overhead. Researchers typically spend 30–50% of their time on grants

 

To me, "overhead" means "I only get to spend 58% of the money I raise, Harvard takes the other 42%".

Comment by Metacelsus on Out-of-distribution Bioattacks · 2023-12-03T17:41:35.959Z · LW · GW

>And even without LLMs, the number of graduate students who would be capable of doing this has been increasing quickly as technological progress and biological infrastructure decrease the difficulty.

Grad student mental health support might be the next big EA cause area.

Comment by Metacelsus on the uni wheel is dumb · 2023-12-02T16:07:39.668Z · LW · GW

To be fair, the amyloid hypothesis seemed promising 20 years ago, and was well worth investigating. It's just that researchers should have investigated alternative hypotheses too.

Still I agree with the other examples.

Comment by Metacelsus on Am I going insane or is the quality of education at top universities shockingly low? · 2023-11-20T15:27:57.188Z · LW · GW

Which means getting government grants, from which the university takes a cut of overhead.

Comment by Metacelsus on [deleted post] 2023-11-13T00:54:53.845Z

I know quite a few researchers working on bioengineered organs, and the fact that some people donate their kidneys does not make those researchers work less hard.

Comment by Metacelsus on Propaganda or Science: A Look at Open Source AI and Bioterrorism Risk · 2023-11-05T14:20:49.816Z · LW · GW

>Much higher than the anthrax attacks you mention. People in biosecurity think that the tails are more like billions dead or the end of civilization. (I'm not sure if I believe them, the public object level cases for this don't seem that amazing due to info-hazard concerns.)

As a biologist who has thought about these kinds of things (and participated in a forecasting group about them), I agree. (And there are very good reasons for not making the object-level cases public!)

Comment by Metacelsus on Genetic fitness is a measure of selection strength, not the selection target · 2023-11-04T22:25:36.375Z · LW · GW

>You can check this out very easily in seconds and verify that you could do the same thing with less effort than you've probably put into some video games.

Indeed. Donating sperm over the Internet costs approximately $125 per donation (most of which is Fedex overnight shipping costs, and often the recipient will cover these) and has about a 10% pregnancy success rate per cycle.

See: https://www.irvinesci.com/refrigeration-medium-tyb-with-gentamicin.html
and https://www.justababy.com/

Comment by Metacelsus on Mission Impossible: Dead Reckoning Part 1 AI Takeaways · 2023-11-01T16:28:34.974Z · LW · GW

See also: Reagan and "The Day After"

Comment by Metacelsus on Will releasing the weights of large language models grant widespread access to pandemic agents? · 2023-10-31T01:54:47.888Z · LW · GW

I agree with the other commenters here: access to Google and NCBI/PubMed should be taken as a control group.

Comment by Metacelsus on What is a Sequencing Read? · 2023-10-25T20:29:38.271Z · LW · GW

"Paired-end reads" is the most common way to phrase it (at least in my experience). One paired-end read comprises both ends and is equivalent to a read pair. I agree that "read pair" may be less confusing.

Comment by Metacelsus on Will no one rid me of this turbulent pest? · 2023-10-17T19:50:30.121Z · LW · GW

I like your idea of exploring "a more detailed breakdown of who exactly might be opposed, and for what reasons.  And then try and figure out which of these sources actually matter the most / are the most real!"

It reminds me of "Is that your true rejection?" https://www.lesswrong.com/posts/TGux5Fhcd7GmTfNGC/is-that-your-true-rejection

Comment by Metacelsus on Will no one rid me of this turbulent pest? · 2023-10-17T16:56:57.699Z · LW · GW

>Same deal for the project to revive Woolly Mammoths -- the awesome documentary "We Are As Gods" is basically a PR campaign for the righteousness of this cause, and a good portrait of a similar movement which is farther along in the PR pipeline.

 

Unfortunately, on this one the hype has outpaced the science. See: https://www.lesswrong.com/posts/ihq24ri5g5svwwmjx/why-i-m-skeptical-of-de-extinction

Comment by Metacelsus on Will no one rid me of this turbulent pest? · 2023-10-16T16:19:58.804Z · LW · GW

>there is a small chance that release of these gene drives could be an x-risk

I disagree (or, at least, I believe that mosquitoes are more of an x-risk than gene drives, although both are extremely small)

Comment by Metacelsus on Will no one rid me of this turbulent pest? · 2023-10-15T14:53:26.014Z · LW · GW

I strongly disagree with bribery, I think it has the potential to cause a huge scandal which is exactly what we don't want here.

Comment by Metacelsus on Will no one rid me of this turbulent pest? · 2023-10-14T21:28:08.057Z · LW · GW

It depends on whether the main political objection is that "GMO's are scary" or that "killing mosquitoes will disrupt ecosystems". (I've heard both objections, but strongly disagree with them).

If you made malaria-resistant mosquitoes, you'd actually have GMO mosquitoes biting people. With a gene drive that prevents female mosquito development, no transgenic mosquitoes would bite people since they would all be male.

Comment by Metacelsus on "Diamondoid bacteria" nanobots: deadly threat or dead-end? A nanotech investigation · 2023-09-30T01:45:23.645Z · LW · GW

Unfortunately, explaining exactly what kind of engineered bacteria could be dangerous is a rather serious infohazard.

Comment by Metacelsus on "Diamondoid bacteria" nanobots: deadly threat or dead-end? A nanotech investigation · 2023-09-30T01:44:37.449Z · LW · GW

Yeah, Woodward was a real trailblazer (interestingly, my undergrad PI was one of his last students)

Comment by Metacelsus on "Diamondoid bacteria" nanobots: deadly threat or dead-end? A nanotech investigation · 2023-09-29T16:18:11.518Z · LW · GW

>For example, in 2003 the Nanoputian project successfully built a nanoscale model of a person out of organic molecules. They used cleverly chosen reaction pathways to produce the upper body, and cleverly chosen reaction pathways to produce the lower body, and then managed to pick the exact right conditions to mix them together in that would bond the two parts together

As a chemist by training, I don't think this is actually that impressive. They basically did a few Sonogashira couplings, which are rather easy reactions (I did them regularly as an undergrad).

If you want something impressive, look at the synthesis of vitamin B12: https://en.wikipedia.org/wiki/Vitamin_B12_total_synthesis

Comment by Metacelsus on "Diamondoid bacteria" nanobots: deadly threat or dead-end? A nanotech investigation · 2023-09-29T15:55:31.858Z · LW · GW

No, but . . . you don't need "diamondoid" technology to make nano-replicators that kill everything. Highly engineered bacteria could do the trick.

Comment by Metacelsus on AI #29: Take a Deep Breath · 2023-09-14T18:12:16.216Z · LW · GW

They invoke the parallel to the Asilomar Conference that banned recombinant DNA research, a ban that despite the huge incentives still effectively stands to this day.

Recombinant DNA research isn't banned – I've been doing it just today, actually. However, it needs to be approved by a biosafety committee (which at my university basically OK's everything that isn't straight-up insane, although it takes a month or so to get approval).

Comment by Metacelsus on Playing the game vs. finding a cheat code · 2023-09-11T21:27:16.114Z · LW · GW

Another example which I can't believe I overlooked: emulating a human brain vs. building an AI with an architecture better suited for computer chips

Comment by Metacelsus on Text Posts from the Kids Group: 2023 I · 2023-09-06T00:57:23.773Z · LW · GW

Things like this make me want to have kids :)

Comment by Metacelsus on The smallest possible button (or: moth traps!) · 2023-09-04T01:19:28.619Z · LW · GW

>the blind idiot god of moth evolution would find a way to elude my traps by pressing an alternate small button to those specific pheromones, in order to power its reproduction. This type of brute force, which grants a stupid and blind enemy the power of adaptation, can be found in battles with cancer, viruses, or pesticides

Interestingly some cockroaches have evolved to perceive sugar as bitter, due to its use as bait in traps: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003998/

Comment by Metacelsus on Digital brains beat biological ones because diffusion is too slow · 2023-08-26T20:56:50.836Z · LW · GW

Agreed. See also https://denovo.substack.com/p/biological-doom for an overview of different types of biological computation.

Comment by Metacelsus on Predicting Virus Relative Abundance in Wastewater · 2023-08-12T21:02:21.563Z · LW · GW

>If you're paying $8k per billion reads

>This will likely go down: Illumina has recently released the more cost effective NovaSeq X, and as Illumina's patents expire there are various cheaper competitors.

Indeed it did go down. Recently I paid $13,000 for 10 billion reads (NovaSeq X, Broad Institute; this was for my meiosis project). So sequencing costs can be much lower than $8K/billion.

Illumina is planning to start offering a 25 billion read flowcell for the NovaSeq X in October; I don't know how much this will cost but I'd guess around $20,000.

ALSO: if you're trying to detect truly novel viruses, using a Kraken database made from existing viral sequences is not going to work! However, many important threats are variants of existing viruses, so those could be detected (although possibly with lower efficiency).

Comment by Metacelsus on Perpetually Declining Population? · 2023-08-08T01:57:42.665Z · LW · GW

Yes, this will definitely be a problem starting in a few decades. Developing technology that can help people have kids (in vitro gametogenesis, and especially artificial wombs) is going to be important. Artificial wombs are harder, but probably more impactful for overall fertility rates in vitro gametogenesis.

 

Will Chertman wrote a very nice whitepaper on fertility last year, but I can't seem to find it now. (edit: here it is: https://docs.google.com/document/d/e/2PACX-1vT1hgf95phUa4e1nqf2VTfjFmUeSBwb7mihE86cU6bE1EI-EZteWm6UmeC18PJSs3Laog4rP7qKtT1j/pub)